1. Field of the Invention
This invention resides in the fields of respiratory distress syndrome, pre-natal and neonatal infant care in general, and lung diseases of both infants and adults. In particular, this invention addresses issues related to the use of naturally-occurring surfactants, modifications of natural surfactants, and synthetic analogs of natural surfactants as therapeutic agents for the treatment of various conditions.
2. Description of the Prior Art
Acute lung injury is a major clinical problem that includes diseases as disparate as acute respiratory distress syndrome in adults, neonatal respiratory distress syndrome, meconium aspiration pneumonia in newborn infants, bacterial and viral pneumonia, pneumonia caused by aspiration of stomach contents, smoke inhalation, and near drowning. Respiratory distress syndrome, for example, is a common disorder in premature infants, and interest in this disorder among pediatricians and pathologists has grown since the 1940s. Within the last twenty years, however, the use of exogenous pulmonary surfactants has emerged as an effective therapy for the treatment and prevention of this disorder. The use of pulmonary surfactants was first reported by Fujiwara and coworkers in 1980 whose studies showed the successful reduction of respiratory distress in preterm infants by the instillation of bovine lung surfactant into the trachea of the infants. Subsequent work by Fujiwara and others has led to the use of a variety of mammalian-derived lung surfactants as therapeutic agents, particularly surfactants that have been extracted, supplemented or otherwise treated to improve their effectiveness. With these advances in surfactant therapy, neonatal deaths and various related lung diseases no longer have the high morbidity rates that they once had.
Unfortunately, a significant percentage of cases fail to respond adequately to surfactant therapy, experiencing instead only a transitory or minimal response. Numerous explanations for this have been offered, each citing the inactivation of surfactant in situ by one or more substances that are normally absent from the alveolar spaces. Aside from the inactivation of exogenous surfactants, endogenous surfactants can be inactivated as well, and this has been implicated as the cause or one of the contributing factors or symptoms of several of the various disease conditions listed in the preceding paragraph. In either case, the substances suspected of causing inactivation include blood, plasma proteins, serum proteins, lipids, and meconium, which is the mass of mucous, desquamated epithelial cells, lanugo, and vernix caseosa that collects in the fetal intestine.
In some cases, inactivation of surfactant, whether exogenous or endogenous, has been reduced by increasing the amount of surfactant relative to the inactivating substance.
Inactivation has also been reduced by the administration or co-administration of the surfactant-associated proteins SP-A, SP-B, and SP-C. These proteins are not readily available, however, since they must either be extracted from naturally-occurring surfactants or synthesized by protein synthesis techniques. Accordingly, the search for substances that are effective in countering the various forms of inactivation continues.